Bortezomib Dendrimer Prodrug‐Based Nanoparticle System

Hu, Xuefeng; Chai, Zhilan; Lu, Linwei; Ruan, Huitong; Wang, Ruifeng; Zhan, Changyou; Xie, Conghua; Pan, Jun; Wang, Ruifeng; Wang, Hao; Lu, Weiyue

doi:10.1002/adfm.201807941

Cited by 42 publications

(33 citation statements)

References 32 publications

(31 reference statements)

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“…However, new delivery strategies such as nanoparticlederived systems may help overcome specificity issues by directing drugs to specific cellular compartments (335). Indeed, preclinical studies have highlighted the effectiveness and potential of bortezomib nanoparticle delivery, with for example anti-CD38 chitosan nanoparticles improving multiple myeloma cell targeting and resulting in a lower toxicity profile (336)(337)(338).…”

Section: Modulating Proteasomal Activitymentioning

confidence: 99%

Targeting the Ubiquitin System in Glioblastoma

et al. 2020

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Glioblastoma is the most common primary brain tumor in adults with poor overall outcome and 5-year survival of less than 5%. Treatment has not changed much in the last decade or so, with surgical resection and radio/chemotherapy being the main options. Glioblastoma is highly heterogeneous and frequently becomes treatment-resistant due to the ability of glioblastoma cells to adopt stem cell states facilitating tumor recurrence. Therefore, there is an urgent need for novel therapeutic strategies. The ubiquitin system, in particular E3 ubiquitin ligases and deubiquitinating enzymes, have emerged as a promising source of novel drug targets. In addition to conventional small molecule drug discovery approaches aimed at modulating enzyme activity, several new and exciting strategies are also being explored. Among these, PROteolysis TArgeting Chimeras (PROTACs) aim to harness the endogenous protein turnover machinery to direct therapeutically relevant targets, including previously considered “undruggable” ones, for proteasomal degradation. PROTAC and other strategies targeting the ubiquitin proteasome system offer new therapeutic avenues which will expand the drug development toolboxes for glioblastoma. This review will provide a comprehensive overview of E3 ubiquitin ligases and deubiquitinating enzymes in the context of glioblastoma and their involvement in core signaling pathways including EGFR, TGF-β, p53 and stemness-related pathways. Finally, we offer new insights into how these ubiquitin-dependent mechanisms could be exploited therapeutically for glioblastoma.

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Section: Modulating Proteasomal Activitymentioning

confidence: 99%

Targeting the Ubiquitin System in Glioblastoma

et al. 2020

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“…[126] Hu et al developed NPs from an amphiphilic PEGylated dendrimer with dopamine and was able to form the conjugate with BTZ, this interaction was weakened at low pH, consequently ensured the constant release of BTZ in the acidic environment of tumor tissues. [127]…”

Section: Ph Responsivementioning

confidence: 99%

Nanoparticulation of Prodrug into Medicines for Cancer Therapy

et al. 2021

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This article provides a broad spectrum about the nanoprodrug fabrication advances co-driven by prodrug and nanotechnology development to potentiate cancer treatment. The nanoprodrug inherits the features of both prodrug concept and nanomedicine know-how, attempts to solve underexploited challenge in cancer treatment cooperatively. Prodrugs can release bioactive drugs on-demand at specific sites to reduce systemic toxicity, this is done by using the special properties of the tumor microenvironment, such as pH value, glutathione concentration, and specific overexpressed enzymes; or by using exogenous stimulation, such as light, heat, and ultrasound. The nanotechnology, manipulating the matter within nanoscale, has high relevance to certain biological conditions, and has been widely utilized in cancer therapy. Together, the marriage of prodrug strategy which shield the side effects of parent drug and nanotechnology with pinpoint delivery capability has conceived highly camouflaged Trojan horse to maneuver cancerous threats.

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“…1c). Furthermore, Hu et al also developed a pH-responsive bortezomib (BTZ) dendrimer prodrug-based nanomedicine, which displayed prominent pH-dependent prototype drugs release behavior and good tumor inhibition [32].…”

Section: Ph-responsivementioning

confidence: 99%

Stimuli-responsive prodrug-based cancer nanomedicine

et al. 2020

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The rapid development of nanotechnology results in the emergence of nanomedicines, but the effective delivery of drugs to tumor sites remains a great challenge. Prodrug-based cancer nanomedicines thus emerged due to their unique advantages, including high drug load efficiency, reduced side effects, efficient targeting, and real-time controllability. A distinctive characteristic of prodrug-based nanomedicines is that they need to be activated by a stimulus or multi-stimulus to produce an anti-tumor effect. A better understanding of various responsive approaches could allow researchers to perceive the mechanism of prodrugbased nanomedicines effectively and further optimize their design strategy. In this review, we highlight the stimuli-responsive pathway of prodrug-based nanomedicines and their anticancer applications. Furthermore, various types of prodrug-based nanomedicines, recent progress and prospects of stimuli-responsive prodrug-based nanomedicines and patient data in the clinical application are also summarized. Additionally, the current development and future challenges of prodrug-based nanomedicines are discussed. We expect that this review will be valuable for readers to gain a deeper understanding of the structure and development of prodrug-based cancer nanomedicines to design rational and effective drugs for clinical use.

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Bortezomib Dendrimer Prodrug‐Based Nanoparticle System

Cited by 42 publications

References 32 publications

Targeting the Ubiquitin System in Glioblastoma

Targeting the Ubiquitin System in Glioblastoma

Nanoparticulation of Prodrug into Medicines for Cancer Therapy

Stimuli-responsive prodrug-based cancer nanomedicine

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